The assignment of human genes to chromosomes has proved difficult when limited to classical Mendelian genetics. A parasexual alternative to conventional methods has been demonstrated by the use of interspecific somatic cell hybrids. Human chromosomes are preferentially lost in proliferating man-mouse and man-Chinese hamster cell hybrids and clones can be isolated with different numbers and combinations of human chromosomes and enzymes. Human gene-chromosome relationships are established when positive correlations are observed for the concurrent loss of specific enzymes and chromosomes. The objective for this proposed research is to assign human genes to chromosomes and, by employing human translocated chromosomes, to map genes to specific segments of human chromosomes. A series of human cells possessing individual translocations involving chromosomes 1, 2, 3, 6, 9, 13, 14, 18, 20, 21, 22, and X will be hybridized to mouse and to Chinese hamster cells. The positive association of two linkage groups and a translocated chromosome can lead to the assignment of genes to specific chromosomes and in fact, to a specific segment of a chromosome. Human chromosomes will be identified by fluorescence and Giemsa banding and heterochromatin staining. Some 40 human enzymes will be tested in the cell hybrids. Several of the enzymes are associated with inherited metabolic diseases including hemolytic anemias and neurodegenerative disorders. The evolutionary significance of human gene linkages will be studied by comparing the gene linkages of other species as determined through interspecific cell hybrids. The expression of translocated genes and a study of the inactive X hypothesis will be investigated with X-autosomal translocations in cell hybrids. A knowledge of gene assignments in man, how the genes are controlled, and why they are coded on a specific chromosome necessary for understanding the biology of man.